The sensation of pain is a common symptom that may be indicative of an underlying disease or injury, or the expression of an abnormal function within the nervous system. Pain is often the primary incentive for which treatment is sought.
Pain can take a variety of forms depending on its origin. Pain may be described as being peripheral neuropathic if the initiating injury occurs as a result of a complete or partial transection of a nerve or trauma to a nerve plexus. Alternatively, pain is described as being central neuropathic following a lesion to the central nervous system, such as a spinal cord injury or a cerebrovascular accident. Inflammatory pain is a form of pain that is caused by tissue injury or inflammation (e.g., in postoperative pain or rheumatoid arthritis). Following a peripheral nerve injury, symptoms are typically experienced in a chronic fashion, distal to the site of injury and are characterized by hyperesthesia (enhanced sensitivity to a natural stimulus), hyperalgesia (abnormal sensitivity to a noxious stimulus), allodynia (widespread tenderness, associated with hypersensitivity to normally innocuous tactile stimuli), and/or spontaneous burning or shooting lancinating pain. In inflammatory pain, symptoms are apparent, at least initially, at the site of injury or inflamed tissues and typically accompany arthritis-associated pain, musculo-skeletal pain, and postoperative pain. Nociceptive pain is the pain experienced in response to a noxious stimulus, such as a needle prick or during trauma or surgery. Functional pain refers to conditions in which there is no obvious peripheral pathology or lesion to the nervous system. This particular form of pain is generated by abnormal function of the nervous system and conditions characterized by such pain include fibromyalgia, tension-type headache, and irritable bowel syndrome. The different types of pain may coexist or pain may be transformed from inflammatory to neuropathic during the natural course of the disease, as in post-herpetic neuralgia.
Although one approach for the treatment of pain is the removal of the causative or etiological agent (disease modifying therapy), the pain often outlasts the duration of the initiating cause. Accordingly, symptomatic control is essential. In cases in which the sensation of pain becomes unbearable, rapid and effective analgesia is imperative (e.g., postoperative state, burns, trauma, cancer, and sickle cell crisis). Currently, there exist a wide variety of analgesic agents useful for the management of pain, including for example non-steroidal analgesic agents (NSAIDs), anticonvulsants, and opioid analgesics. Despite their efficacy, the chronic use of such agents is often not recommended because of the potential debilitating side effects, such as gastric irritation, toxicity to the liver, respiratory depression, sedation, psychotomimetic effects, constipation, nausea, tolerance, dependence, and the risk of abuse. Also, these agents are sometimes suboptimal, particularly for neuropathic and functional pain.
Thus, better therapeutic strategies are required for the treatment and management of pain.